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胰岛素抵抗与TZDs类药物
——Spanheimer博士专访
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专家访谈 作者:Spanheimer博士 来源:未知 2010/12/8 17:29:00    加入收藏
内容概要:胰岛素抵抗是指胰岛素不能有效应答,而胰岛素的作用之一是脂肪的恰当分布。我们进餐后,胰岛素帮助我们指挥脂肪如何分布。如果有胰岛素抵抗则不能获得胰岛素这样的生物学作用,脂肪不能正常的代谢和分布。

  International Diabetes: How does insulin resistance affect the development of dylipidemia?
  Dr. Spanheimer: Insulin resistance is the inability to respond effectively to insulin and one of the actions of insulin is to distribute fat appropriately. After we eat a meal, insulin helps us to direct fat where it should go. If you have insulin resistance you do not get the same biologic effects of insulin and that fat is not processed and distributed as it should be. Therefore, insulin is very important in fat metabolism.
  International Diabetes: Metformin is often viewed as an insulin sensitizer. What is the difference between metformin and pioglitazone with regard to improving insulin resistance?
  Dr. Spanheimer: Pioglitazone is a true insulin sensitizer. If you add it to cells in a dish and add insulin you see biologic effects inside cells and you do not see that with metformin. Metformin probably indirectly improves insulin sensitivity by reducing glucose. Any diabetic medication that lowers blood sugar appears to improve insulin resistance but TZDs are the only direct insulin sensitizers.
  International Diabetes: Does pioglitazone have more favorable effects on serum lipids than rosiglitazone?
  Dr. Spanheimer: Physicians were telling us that their patients on pioglitazone were having a different response than their patients on rosiglitazone. As a result, there was a double-blind randomized clinical trial designed to study this phenomenon. Patients were randomized to receive either the maximum does of rosiglitzone or the maximum does of pioglitazone and were followed for 24 weeks. At the end of that time there were significant differences in serum lipids in the patients treated with pioglitazone compared to rosiglitazone. At the end of the trial patients on rosiglitazone had a 27% higher triglyceride level and they less of an increase in HDL cholesterol, with pioglitazone having twice the response of rosiglitazone in raising HDL.
  International Diabetes: Do you think that the positive cardiovascular effects of TZDs, including reduced hyperglycemia, improved dyslipidemia, and reduced central obesity outweigh the negative effects such as weight gain?
  Dr. Spanheimer: That is a difficult question. What I prefer to do is give physicians both the beneficial effects and side-effects of this class of drugs. Physicians know their patients and what they are comfortable with and if you give them the pertinent safety and efficacy information they can make the best decisions for their patients.
  International Diabetes: In the lectures today there was an emphasis on combination therapy early in treatment. What do you think of the potential for a combination of TZDs with some of the new agents such as GLP-1 analogues?
  Dr. Spanheimer:  We do not know enough about GLP-1 analogues in combination because they are too new. When a new drug comes on the market you need to find out what it does alone. You must asses it in monotherapy and get clinical experience with the drug alone before adding it in combination. In the United States we have seen that patients started on one drug soon fail. However, when you combine it with another drug you seem to prolong the beneficial effect of the combination because you are using two different mechanisms. Since we are seeing that patients often fail their first drug and need a second one, it has caused some physicians to want to know about the early use of different combinations. There are physicians in the US advocating early use of the combination with GLP-1 drugs, but the data is not yet available to support it.
  《国际糖尿病》:胰岛素抵抗如何对血脂产生影响?
  Spanheimer博士:胰岛素抵抗是指胰岛素不能有效应答,而胰岛素的作用之一是脂肪的恰当分布。我们进餐后,胰岛素帮助我们指挥脂肪如何分布。如果有胰岛素抵抗则不能获得胰岛素这样的生物学作用,脂肪不能正常的代谢和分布。因此,胰岛素对脂肪代谢非常重要。
  《国际糖尿病》:二甲双胍通常被看作是胰岛素增敏剂。在改善胰岛素抵抗方面,二甲双胍和吡格列酮的区别有哪些?
  Spanheimer博士: 吡格列酮是一种真正的胰岛素增敏剂。如果在细胞的培养皿中添加吡格列酮和胰岛素,你可以观察到细胞内的生物学效应;但二甲双胍不能。二甲双胍可以通过降低血糖间接改善胰岛素敏感性。任何降低血糖的糖尿病药物都可以改善胰岛素抵抗,但TZDs是唯一的直接胰岛素增敏剂。
  《国际糖尿病》:吡格列酮对血脂的作用是否优于罗格列酮?
  Spanheimer博士:医生告诉我们使用吡格列酮的患者的反应与使用罗格列酮的患者不同。因此为此,我们设计了一项双盲随机临床试验来研究这一现象。该研究中患者随机接受最大剂量的罗格列酮或者最大剂量的吡格列酮治疗,并随访24周。在试验结束时,使用吡格列酮治疗的患者其的血脂水平与使用罗格列酮治疗的患者显著不同。在研究终点时,使用罗格列酮的患者甘油三酯水平升高27%,HDL胆固醇水平的增加不多,而使用吡格列酮的患者HDL水平的增加是罗格列酮治疗的患者的两倍。
  《国际糖尿病》:您认为TZDs对心血管方面的正性作用,包括降糖、调脂、减少中心性肥胖等,是否要大于其不良作用,如体重增加?
  Spanheimer博士:这是一个很难回答的问题。我的倾向是告诉医生这类药物的好的作用及其副作用我的倾向是告诉医生这类药物有益的作用及其副作用。医生会了解他们的患者以及并知道患者的需要,如果告诉他们相关的安全性和有效性的信息,他们会为患者作出最佳选择。
  《国际糖尿病》:在今天的讲演中强调了早期联合治疗。您如何看待TZDs与与一些新的药物的联合使用的前景,如GLP-1类似物?
  Spanheimer博士:我们确实不很了解胰高血糖素样肽(GLP-1)类似物的联合应用,因为这是一类比较新的类药物太新了。当一种新药出现在市场上,你需要了解它自己是什么样子你需要了解它的特性。在联合使用之前,你必须对其单药治疗进行评估,并获取临床经验。在美国,我们已经看到患者单药治疗迅速失效。然而,当与其他药物联合使用时,可以延长联合治疗的疗效,因为使用了两种不同的机制因为通过两种不同的机制发挥作用。既然我们发现患者第一种药物治疗通常失败失效而需要加用第二种药物,这使得一些医生想要知道不同的联合用药的早期应用。在美国一些医生支持早期联合使用GLP-1药物,但还没有充分的数据的充分支持。

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